Heterodimeric insecticidal peptide provides new insights into the molecular and functional diversity of ant venoms
Heterodimeric insecticidal peptide provides new insights into the molecular and functional diversity of ant venoms
Abstract Ants use venom for predation, defence and communication, however, the molecular diversity, function and potential applications of ant venom remains understudied compared to other venomous lineages such as arachnids, snakes and cone snails. In this work, we used a multidisciplinary approach that encompassed field work, proteomics, sequencing, chemical synthesis, structural analysis, molecular modelling, stability studies, and a series of in vitro and in vivo bioassays to investigate the molecular diversity of the venom of the Amazonian Pseudomyrmex penetrator ants. We isolated a potent insecticidal heterodimeric peptide Δ-pseudomyrmecitoxin-Pp1a (Δ-PSDTX-Pp1a) composed of a 27-residue long A-chain and a 33-residue long B-chain crosslinked by two disulfide bonds in an antiparallel orientation. We chemically synthesised Δ-PSDTX-Pp1a, its corresponding parallel AA and BB homodimers, and its monomeric chains and demonstrated that Δ-PSDTX-Pp1a had the most potent insecticidal effects in blow fly assays (LD50 = 3 nM). Molecular modelling and circular dichroism studies revealed strong alpha-helical features, indicating its cytotoxic effects could derive from membrane disruption, which was further supported by insect cell calcium assays. The native heterodimer was also substantially more stable against proteolytic degradation (t1/2 =13 h) than its homodimers or monomers (t1/2 <20 min), indicating an evolutionary advantage of the more complex structure. The proteomic analysis of Pseudomyrmex penetrator venom and in-depth characterisation of Δ-PSDTX-Pp1a provide novel insights in the structural complexity of ant venom, and further exemplifies how nature exploits disulfide-bond formation and dimerization to gain an evolutionary advantage via improved stability; a concept that is also highly relevant for the design and development of peptide therapeutics, molecular probes and bioinsecticides.
King Glenn F.、B¨|roud R¨|my、Delalande Olivier、Mendel Helen C.、Dejean Alain、Duplais Christophe、Jaquillard Lucie、Touchard Axel、Muttenthaler Markus、Triquigneaux Mathilde、Emidio Nayara Braga、Boulogne Isabelle、De Waard Michel、Herzig Volker
Institute for Molecular Bioscience, The University of QueenslandSmartox BiotechnologyInstitute of Genetics and Development of Rennes (IGDR), CNRS UMR 6290, Universit¨| de Rennes Facult¨| de Pharmacie, 2 avenue du Professeur L¨|on BernardInstitute for Molecular Bioscience, The University of QueenslandCNRS, UMR Ecofog, AgroParisTech, Cirad, INRAE, Universit¨| des Antilles, Universit¨| de Guyane||Ecolab, Universit¨| de Toulouse, CNRS, INPT, UPSCNRS, UMR Ecofog, AgroParisTech, Cirad, INRAE, Universit¨| des Antilles, Universit¨| de GuyaneSmartox BiotechnologyCNRS, UMR Ecofog, AgroParisTech, Cirad, INRAE, Universit¨| des Antilles, Universit¨| de GuyaneInstitute for Molecular Bioscience, The University of Queensland||Institute of Biological Chemistry, Faculty of Chemistry, University of ViennaSmartox BiotechnologyInstitute for Molecular Bioscience, The University of QueenslandUniversit¨| de ROUEN, UFR des Sciences et Techniques, Laboratoire Glycobiologie et Matrice Extracellulaire V¨|g¨|tale, UPRES-EA 4358, F¨|d¨|ration de Recherche ? Normandie V¨|g¨|tal ?Smartox Biotechnology||Universit¨| de Nantes, CNRS, INSERM, L?ˉinstitut du thorax||LabEx ?Ion Channels, Science & Therapeutics?Institute for Molecular Bioscience, The University of Queensland||School of Science and Engineering, University of the Sunshine Coast
分子生物学昆虫学生物科学研究方法、生物科学研究技术
Ant venomDisulfide bondHeterodimeric toxinCytotoxicityInsecticide properties
King Glenn F.,B¨|roud R¨|my,Delalande Olivier,Mendel Helen C.,Dejean Alain,Duplais Christophe,Jaquillard Lucie,Touchard Axel,Muttenthaler Markus,Triquigneaux Mathilde,Emidio Nayara Braga,Boulogne Isabelle,De Waard Michel,Herzig Volker.Heterodimeric insecticidal peptide provides new insights into the molecular and functional diversity of ant venoms[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/2020.07.29.226878.点此复制
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